Effect of diterpenoid kaurenoic acid on genotoxicity and cell cycle progression in gastric cancer cell lines

Effect of diterpenoid kaurenoic acid on genotoxicity and cell cycle progression in gastric cancer cell lines

Author dos Santos Cardoso, Plinio Cerqueira Google Scholar
Machado da Rocha, Carlos Alberto Google Scholar
Leal, Mariana Ferreira Autor UNIFESP Google Scholar
Bahia, Marcelo de Oliveira Google Scholar
Avila Alcantara, Diego Di Felipe Google Scholar
dos Santos, Raquel Alves Google Scholar
Goncalves, Natalia dos Santos Google Scholar
Ambrosio, Sergio Ricardo Google Scholar
Cavalcanti, Bruno Coelho Google Scholar
Moreira-Nunes, Caroline Aquino Google Scholar
Pessoa, Claudia do O. Google Scholar
Rodriguez Burbano, Rommel Mario Google Scholar
Abstract The goal of our study was to evaluate the effect of kaurenoic acid, obtained from copaiba oil resin, in gastric cancer (GC) and a normal mucosa of stomach (MNP01) cell lines. The compound was tested at concentrations of 2.5, 5, 10, 30 and 60 mu g/mL. Comet and micronucleus assays were used to access its potential genotoxicity in vitro. Moreover, we evaluated the effect of kaurenoic acid in cell cycle progression and in the transcription of genes involved in the control of the cell cycle: MYC, CCND1, BCL2, CASP3, ATM, CHK2 and TP53. Kaurenoic acid induced an increase on cell DNA damage or micronucleus frequencies on GC cell lines in a dose-dependent manner. The GC and MNP01 cell lines entering DNA synthesis and mitosis decreased significantly with kaurenoic acid treatment, and had an increased growth phase compared with non-treated cells. The treatment induced apoptosis (or necrosis) even at a concentration of 2.5 mu g/mL in relation to non-treated cells. GC cell lines presented reduced MYC, CCND1, BCL2 and CASP3 transcription while ATM, CHK2 and TP53 increased in transcription in relation to nontreated cells, especially at a concentration above 10 mu g/mL. The gene transcription in the MNP01 (nontreated non-cancer cell line) was designated as a calibrator for all the GC cell lines. In conclusion, our results showed that kaurenoic acid obtained from Copaifera induces DNA damage and increases the micronuclei frequency in a dose-dependent manner in GC cells, with a significant genotoxicity observed above the concentration of 5 mu g/mL. Moreover, this compound seems to be able to induce cell cycle arrest and apoptosis in GC cells. (C) 2017 Elsevier Masson SAS. All rights reserved.
Keywords Cell cycle progression
Comet assay
Gastric cancer cell lines
Gene transcriptions
Kaurenoic acid
Micronuclei
xmlui.dri2xhtml.METS-1.0.item-coverage Paris
Language English
Sponsor Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
Date 2017
Published in Biomedicine & Pharmacotherapy. Paris, v. 89, p. 772-780, 2017.
ISSN 0753-3322 (Sherpa/Romeo, impact factor)
Publisher Elsevier France-Editions Scientifiques Medicales Elsevier
Extent 772-780
Origin http://dx.doi.org/10.1016/j.biopha.2017.02.085
Access rights Closed access
Type Article
Web of Science ID WOS:000402468200088
URI https://repositorio.unifesp.br/handle/11600/54568

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